title: The design, synthesis and biological evaluation of 7-alkoxy-4-heteroarylamino-3-cyanoquinolines as dual inhibitors of c-Src and iNOS.
abstract: Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heterocycle amine-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, synthesized and evaluated as multiple targets agents in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds inhibited c-Src and iNOS well. The best compound 8 inhibited both enzymes with the IC(50) values of 34.8 nM and 26.7 microM. Several compounds also showed moderate anti-proliferation at 10 microM against colon and liver cancer cell lines.
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
authors.forename: Qi-Dong
authors.initials: QD
authors.lastname: You
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Li
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Qing-Long
authors.initials: QL
authors.lastname: Guo
authors.forename: Jing
authors.initials: J
authors.lastname: Shang
authors.forename: Ji-Wang
authors.initials: JW
authors.lastname: Chern
authors.forename: Meng-Ling
authors.initials: ML
authors.lastname: Chen
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000081247:CSK Tyrosine-Protein Kinase; D015195:Drug Design; D019073:HT29 Cells; D006801:Humans; D015394:Molecular Structure; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D019061:src-Family Kinases
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C471992:bosutinib; D052247:Nitric Oxide Synthase Type II; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human